Our overall goal is to delineate the mechanism(s) whereby dietary polyunsaturated fatty acids exert an influence on the growth of mammary adenocarcinomas. The mouse mammary gland-tumor system will be used as the model since three distinct stages of tumorigenesis are easily identifiable: a) transformation of normal mammary epithelia into inapparent transformed cells; b) appearance of preneoplastic, hyperplastic alveolar nodules (HAN) derived from inapparent transformed cells; and c) development of HAN into frank neoplasms. Transplantable mammary adenocarcinomas will be used to determine whether observed increases in tumor mass are caused by: a) linoleate and/or its metabolic products; b) specific prostaglandins derived from linoleate or arachidonate; c) either a reduced tumor cell loss or an increased tumor cell proliferation; d) the immune system and, if so, by which specific immune cell population having defineable characteristics; and e) a mechanism of action in which linoleate effects enzyme activities associated with differentiation or function of a specific immune cell population. The use of transplactable neoplasms will simplify interpretation of results since only neoplastic promotion and not initiation will be involved. The techniques used in this program will include the determination of cell cycle parameters, and those commonly associated with immunology and enzymology. The BALB/cfC3H mouse, a high mammary tumor incidence strain infected with the mammary tumor virus, will be used to study the effects of dietary linoleate on the three stages of tumorigenesis. Additional techniques used will include a) cell dissociation and implantation of such cells into cleared fat pads, b) serial propagation of HAN and c) cell culture of neoplastic and preneoplastic (HAN) cells.